Modes of Interactions with DNA/HSA Biomolecules and Comparative Cytotoxic Studies of Newly Synthesized Mononuclear Zinc(II) and Heteronuclear Platinum(II)/Zinc(II) Complexes toward Colorectal Cancer Cells

Sep 21, 2026

A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4′,4′′-tri-tertbutyl-2,2′:6′,2′′-terpyridine were synthesized and characterized. DNA and protein binding were assessed using electronic absorption, fluorescence spectroscopy, and molecular docking. Complexes with transplatin showed lower Kb and Ksv than cisplatin analogs, with C1 having the lowest Ksv and C4 the highest. Docking indicates C1–DNA binding via van der Waals forces, while C2–C5 involve hydrogen bonds and van der Waals interactions. The complexes displayed variable cytotoxicity toward colorectal cancer cells (CT26, HCT116, SW480) and non-cancerous mMSC, with C1 showing pronounced cancer selectivity and inducing apoptosis and G0/G1 arrest with Cyclin D down-regulation.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages27

Reading Time1 h 8 min

AccessFree to download

Introduction

Synthesis and Characterization

DNA and Protein Binding Studies

Molecular Docking Analysis

Cytotoxicity and Mechanistic Evaluation

Article Modes of Interactions with DNA/HSA Biomolecules and Comparative Cytotoxic Studies of Newly Synthesized Mononuclear Zinc(II) and Heteronuclear Platinum(II)/Zinc(II) Complexes toward Colorectal Cancer Cells Samir Vuˇcelj 1,2, Rušid Hasi´c 3, Darko Ašanin 4, Biljana Šmit 4, Angelina Cakovi´c 5, Jovana Bogojeski 5, Marina ´Cendi´c Serafinovi´c 5, Bojana Simovi´c Markovi´c 1, Bojan Stojanovi´c 1,6, Sladjana Pavlovi´c 1, Isidora Stanisavljevi´c 1, Irfan ´Corovi´c 1,2, Milica Dimitrijevi´c Stojanovi´c 1,7, Ivan Jovanovi´c 1, Tanja V. Soldatovi´c 3, * and Bojana Stojanovi´c 1,8 Citation: Vuˇcelj, S.; Hasi´c, R.; Ašanin, D.; Šmit, B.; Cakovi´c, A.; Bogojeski, J.; Serafinovi´c, M.´C .; Markovi´c, B.S.; Stojanovi´c, B.; Pavlovi´c, S.; et al. Modes of Interactions with DNA/HSA Biomolecules and Comparative Cytotoxic Studies of Newly Synthesized Mononuclear Zinc(II) and Heteronuclear Platinum(II)/Zinc(II) Complexes toward Colorectal Cancer Cells. Int. J. Mol. Sci. 2024, 25, 3027. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25053027](doi.org/10.3390/ijms25053027) Academic Editor: Antonio Carrieri Received: 27 January 2024 Revised: 13 February 2024 Accepted: 15 February 2024 Published: 6 March 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, University of Kragujevac, S. Markovi´ca 69, 34000 Kragujevac, Serbia; [vucelj.samir@hotmail.com](vucelj.samir@hotmail.com) (S.V.); [bojana.simovic@gmail.com](bojana.simovic@gmail.com) (B.S.M.); [bojan.stojanovic01@gmail.com](bojan.stojanovic01@gmail.com) (B.S.); [sladjadile@gmail.com](sladjadile@gmail.com) (S.P.); [isidorastanisavljevic97@gmail.com](isidorastanisavljevic97@gmail.com) (I.S.); [ira.corovic@gmail.com](ira.corovic@gmail.com) (I.´C .); milicadimitrijevic@yahoo.com (M.D.S.); [ivanjovanovic77@gmail.com](ivanjovanovic77@gmail.com) (I.J.); [bojana.stojanovic04@gmail.com](bojana.stojanovic04@gmail.com) (B.S.) 2 General Hospital of Novi Pazar, Department of Internal Medicine, Generala Živkovi´ca 1, 36300 Novi Pazar, Serbia 3 Department of Natural-Mathematical Sciences, State University of Novi Pazar, Vuka Karadži´ca 9, 36300 Novi Pazar, Serbia; [rusid.np.chem@gmail.com](rusid.np.chem@gmail.com) 4 Institute for Information Technologies, University of Kragujevac, Jovana Cviji´ca bb, 34000 Kragujevac, Serbia; [darko.asanin@uni.kg.ac.rs](darko.asanin@uni.kg.ac.rs) (D.A.); [biljana.smit@uni.kg.ac.rs](biljana.smit@uni.kg.ac.rs) (B.Š .) 5 Faculty of Science, University of Kragujevac, Radoja Domanovi´ca 12, 34000 Kragujevac, Serbia; [angelina.petrovic@pmf.kg.ac.rs](angelina.petrovic@pmf.kg.ac.rs) (A.C.); [jovana.bogojeski@pmf.kg.ac.rs](jovana.bogojeski@pmf.kg.ac.rs) (J.B.); [marina.cendic@pmf.kg.ac.rs](marina.cendic@pmf.kg.ac.rs) (M.´C .S.) 6 Faculty of Medical Sciences, Department of Surgery, University of Kragujevac, S. Markovi´ca 69, 34000 Kragujevac, Serbia 7 Faculty of Medical Sciences, Department of Pathology, University of Kragujevac, S. Markovi´ca 69, 34000 Kragujevac, Serbia 8 Faculty of Medical Sciences, Department of Pathophysiology, University of Kragujevac, S. Markovi´ca 69, 34000 Kragujevac, Serbia * Correspondence: [tsoldatovic@np.ac.rs](tsoldatovic@np.ac.rs) Abstract: A series of mono-and heteronuclear platinum(II) and zinc(II) complexes with 4,4′,4′′-tri-tertbutyl-2,2′ :6′,2′′-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl 2(terpytBu )](C1), [{cis-PtCl(NH 3)2 (µ-pyrazine)ZnCl(terpytBu )}](ClO 4)2 (C2),[{trans-PtCl(NH 3)2 (µ-pyrazine)ZnCl(terpytBu )}](ClO 4)2 (C3), [{cis-P

FAQs

What complexes were synthesized and how were they characterized?

The study synthesized mono- and heteronuclear platinum(II) and zinc(II) complexes based on a 4,4′,4′′-tri-tertbutyl-terpyridine ligand. They were characterized and then evaluated for DNA and protein binding and for biological cytotoxic effects.

How did transplatin complexes compare with cisplatin analogs in binding parameters?

Transplatin featuring complexes showed lower Kb and Ksv values than cisplatin analogs. The lowest Ksv value was for complex C1, while complex C4 had the highest.

Which complex showed the strongest selective cytotoxicity toward cancer cells and what mechanism was observed?

Complex C1 exhibited pronounced selectivity toward cancer cells compared with non-cancerous mMSC. It induced apoptosis in CT26 cells, arrested the cell cycle in G0/G1, and selectively down-regulated Cyclin D.

Sep 21, 2026

Uploaded by Lucas Martin